This project is concerned with clarifying the roles of insulin and growth hormone in regulating the generation of Somatomedin (Sm). Sm is defined as a number of peptides which, putatively, mediate physiologic growth. To date, it has been shown that Sm is generated from liver (and other tissue) and that its presence in serum is dependent on the pressure of biologically active growth hormone and/or insulin. Sm has been detected by a number of bioassays and specific radioassays. This proposal seeks to identify a tissue culture system derived from rat liver which generates bioassayable Sm. The influence of growth hormone and insulin in this system could clarify the mechanisms of Sm generation. The degree to which insulin and growth hormone regulate this process and the specificity of this tissue response with respect to the synthesis of other proteins could be studied. A number of permanent liver cell line as well as primary rat hepatocyte cultures will be studied. Assay methods will initially be bioassay for Multiplication Stimulation Activity (MSA) and eventually radioassay for pertinent peptides will be used. Alpha 2U globulin, a rat hepatic protein which is known responsive to growth hormone, is a non-somatomedin protein which is being studied in vivo. This system may provide valuable insite into growth hormone action.